Multiplex PCR-Based Detection of Circulating Tumor Cells in Lung Cancer Patients Using CK19, PTHrP, and LUNX Specific Primers

Katseli, Anastasia; Maragos, Haralampos; Nezos, Adrianos; Syrigos, Konstantinos; Koutsilieris, Michael

doi:10.1016/j.cllc.2013.04.007

Cited by 16 publications

(12 citation statements)

References 44 publications

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“…It is conceivable that malignancy-associated changes in expression of BPIFA1 reflect the state of differentiation or the malignant cell type. Although BPIFA1 is normally undetectable outside of the respiratory tract, it was detected in lymph nodes, circulating metastatic cells, and pleural effusions of patients with advanced respiratory malignancies, including some non-small cell carcinomas and nasopharyngeal carcinoma (38,45,(78)(79)(80)(81)(82). In this context, BPIFA1 detection likely represents respiratory epithelial-derived metastatic cells.…”

Section: Malignanciesmentioning

confidence: 99%

Bactericidal/Permeability-Increasing Protein Fold–Containing Family Member A1 in Airway Host Protection and Respiratory Disease

Britto

Cohn

2015

Am J Respir Cell Mol Biol

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Section: Malignanciesmentioning

confidence: 99%

Bactericidal/Permeability-Increasing Protein Fold–Containing Family Member A1 in Airway Host Protection and Respiratory Disease

Britto

Cohn

2015

Am J Respir Cell Mol Biol

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“…Here, we present for the first time, a method for identifying circulating cancer stem cells (CCSCs) in the blood of colon cancer patients, using a combination of epithelial cell markers and cancer stem cell markers, such as DCLK1 [ 12 – 14 ], LGR5 [ 15 , 16 ] and CD44 [ 14 , 17 ]. Epithelial cell surface marker CK19 [ 18 , 19 ] and epithelial cell adhesion membrane protein, EpCAM [ 20 ], were used to confirm epithelial origin of the isolated CCSCs; combining surface markers has been shown to increase accuracy of detecting CTCs [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Methods for detecting circulating cancer stem cells (CCSCs) as a novel approach for diagnosis of colon cancer relapse/metastasis

Kantara

O’Connell

Luthra

et al. 2015

Laboratory Investigation

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Cancer stem cells (CSCs) are believed to be resistant to currently available therapies and maybe responsible for relapse of cancer in patients. Measuring circulating tumor cells (CTCs) in blood of patients has emerged as a non-invasive diagnostic procedure for screening patients who may be at high risk for developing metastatic cancers or relapse of the cancer disease. However, accurate detection of CTCs has remained a problem, since epithelial-cell-markers used to-date, are not always reliable for detecting CTCs, especially during epithelial-mesenchymal-transition. Since CSCs are required to initiate metastatic tumors, our goal was to optimize and standardize a method for identifying circulating CSCs (CCSCs) in patients, using established CSC markers. Here, we report for the first time the detection of CCSCs in blood of athymic nude mice, bearing metastatic tumors, and in the blood of patients positive for colonic adenocarcinomas. Using a simple and non-expensive method, we isolated a relatively pure population of CSCs (CD45−/CK19+), free of red blood cells and largely free of contaminating CD45+ white blood cells. Enriched CCSCs from patients with colon adenocarcinomas had a malignant phenotype and co-expressed CSC markers (DCLK1/LGR5) with CD44/Annexin A2. CSCs were not found in the blood of non-cancer patients, free of colonic growths. Enriched CCSCs from colon cancer patients grew primary spheroids, suggesting presence of tumor-initiating cells in the blood of these patients. In conclusion, we have developed a novel diagnostic assay for detecting CSCs in circulation, which may more accurately predict the risk of relapse or metastatic disease in patients. Since CSCs can potentially initiate metastatic growths, patients positive for CCSCs can be treated with inhibitory agents that selectively target CSCs, besides conventional treatments, to reduce the risk of relapse/metastatic disease for improving clinical outcomes.

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“…[ 20 21 ] The detection of CTCs has been well demonstrated in breast, lung, colon, prostate, and bladder cancers, melanoma, and other malignancies. [ 22 23 24 25 26 ] Although CTC detection can contribute to tumor diagnosis and help identify patients with advanced bladder cancer, such assays cannot be used as initial screening diagnostic tests due to their low sensitivity. [ 27 ] PCR-based methods are commonly used, rapid, and low-cost methods for detecting CTCs.…”

Section: Discussionmentioning

confidence: 99%

Expression and Clinical Significance of Cytokeratin-19 and Thymidine Kinase-1 in Advanced Gastrointestinal Cancer

Zhang

Sun

2016

Chinese Medical Journal

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Background:As the clinical value of cytokeratin-19 (CK19) and thymidine kinase-1 (TK1) in advanced gastrointestinal cancer remains controversial, we investigated their expression and clinical significance in this disease.Methods:A total of 171 advanced gastrointestinal cancer patients were prospectively enrolled in this study. The mRNA level of CK19 was detected using quantitative real-time reverse transcription-polymerase chain reaction (PCR) in all patients, along with a control group of fifty healthy individuals. Furthermore, detection of TK1 protein was carried out in 96 patients using a chemiluminescence dot blot assay. The primary endpoint was overall survival (OS) time.Results:Positive CK19 mRNA expression was detected in 74 (43.3%) of the 171 patients and positive TK1 expression was detected in 66 (68.8%) of the 96 patients. Furthermore, of the 96 patients, 36 (37.5%) were positive for both TK1 protein and CK19 mRNA, 30 (31.3%) were negative for TK1 protein, and 15 (15.6%) were negative for TK1 protein and positive for CK19 mRNA. The results indicated that patients who were positive for CK19 mRNA expression had significantly shorter OS times than those who were negative for it (median OS 7.7 vs. 9.7 months, respectively; P = 0.02). Moreover, patients who were positive for CK19 mRNA and TK1 protein expression had shorter OS times (median OS 6.1 months) than those who were positive for CK19 mRNA and negative for TK1 protein expression (median OS 9.1 months; P = 0.028). Positive CK19 mRNA expression was significantly associated with shorter OS in the univariate analysis (P = 0.027). Based on a multivariate Cox regression analysis, CK19 mRNA together with TK1 protein expression (P = 0.024) was an independent predictor for OS in gastrointestinal cancer patients.Conclusions:Our results suggest that positive expression of CK19 mRNA and TK1 protein is closely correlated with poor prognosis in advanced gastrointestinal cancer. Furthermore, both CK19 and TK1 are possible gastrointestinal cancer biomarkers.

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Multiplex PCR-Based Detection of Circulating Tumor Cells in Lung Cancer Patients Using CK19, PTHrP, and LUNX Specific Primers

Cited by 16 publications

References 44 publications

Bactericidal/Permeability-Increasing Protein Fold–Containing Family Member A1 in Airway Host Protection and Respiratory Disease

Bactericidal/Permeability-Increasing Protein Fold–Containing Family Member A1 in Airway Host Protection and Respiratory Disease

Methods for detecting circulating cancer stem cells (CCSCs) as a novel approach for diagnosis of colon cancer relapse/metastasis

Expression and Clinical Significance of Cytokeratin-19 and Thymidine Kinase-1 in Advanced Gastrointestinal Cancer

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